基础医学与临床 ›› 2007, Vol. 27 ›› Issue (4): 402-407.

• 研究论文 • 上一篇    下一篇

骨髓间充质干细胞治疗急性心肌梗塞的实验研究

刘煜昊 方五旺 叶飞   

  1. 中国医学科学院基础医学组织工程中心 中国医学科学院基础医学组织工程中心 中国医学科学院基础医学组织工程中心
  • 收稿日期:2005-11-03 修回日期:2006-06-21 出版日期:2007-04-25 发布日期:2007-04-25
  • 通讯作者: 刘煜昊

Safety and feasibility of autologous bone marrow mesenchymal stem cell transplantation for acute myocardial infarction in pig

  

  • Received:2005-11-03 Revised:2006-06-21 Online:2007-04-25 Published:2007-04-25

摘要: 目的 研究自体骨髓间充质干细胞(MSC)经冠脉内注射治疗急性心肌梗死(AMI)的有效性和可行性。方法 球囊阻塞法制成AMI模型。经冠脉注入标记的MSC,4周后核素心肌断层显像检测相对心肌梗死面积、心肌灌注评分和射血分数,经导管检测左室收缩压(LVSP)、左室舒张末压(LVEDP)、压力升高最大速率(+dP/dt)和压力下降最大速率(-dP/dt)。免疫荧光法分析MSC的植入和分化。结果 与对照组相比,细胞治疗组射血分数显著增加(p<0.05),心肌灌注评分(p<0.01)和相对心肌梗死面积(p<0.05)显著降低,LVSP(p<0.05)、+dP/dt(p<0.01)和-dP/dt(p<0.01)显著增加,LVEDP显著降低(p<0.05)。标记的MSC在心肌中阳性表达肌凝蛋白重链、连接蛋白43、平滑肌肌动蛋白和Ⅷ因子相关抗原。结论 MSC在体内分化为心肌和血管组织,可改善AMI猪的心功能。

Abstract: Objective To test the feasibility and safety of autologous bone marrow mesenchymal stem cell (MSC) transplantation by intracoronary injection in acute myocardial infarcted pig (AMI). Methods Coronary occlusion with balloon was used to produce AMI.Labeled MSCs were implanted by intracoronary injection.Four weeks after AMI,single photon emission computed tomography was used to evaluate the relative infarct size,myocardial perfusion score and ejection fraction (EF) of the animals. Left ventricular systolic pressure( LVSP), left end-diastolic pressure (LVEDP), peak rate of pressure rise(+dP/dt) and peak rate of pressure fall (-dP/dt) were assessed by catheterization. Immunofluorescence was performed to evaluate MSC engrafment and differentiation. Results Compared with control group, heart function parameters were all improved in pigs receiving MSCs transplantation, including EF [(44.1±4.3)% vs (39.0±5.2)%, p<0.05] perfusion score (30.0±5.3 vs 41.8±8.8, p<0.01), relative infarct size[(28.6±4.7)% vs (33.5±3.4)%, p<0.05], LVSP(87.1±8.7mmHg vs 78.0±4.4 mmHg, p<0.05), +dP/dt(1818.1±116.7mmHg/s vs 1610.6±114.5 mmHg/s, p<0.01) , -dP/dt(1800.9±88.5mmHg/s vs 1618.4±65.7 mmHg/s, p<0.01) and LVEDP(9.4±1.7mmHg vs 12.6±2.8 mmHg, p<0.05). MSCs implanted in myocardium were stained positively for myosin heavy chain, connexin 43, smooth muscle actin and von Willebrand factor. Conclusions Transplantation of MSCs could improve cardiac function in AMI pig, and that the improvement might result from myocardial regeneration and angiogenesis by MSC differentiation.